The objective of this research is to characterize the molecular structure and stabilizing interactions of the membranes comprising the myelin sheath. The structural neuropathology of myelin will be studied by coordinated X-ray diffraction, thin-section and freeze-fracture electron microscopy, electron probe X-ray microanalysis, and chemical analysis. Measurements will be made on intact myelin, on membranes purified from myelin of the central and peripheral nervous system, and on model systems constituted from specific myelin lipids and proteins. Analysis of myelin in normal and pathological tissue, in neurological mutants with defined myelin abnormalities, and in animals with induced demyelination will yield information on the protein and lipid interactions which stabilize the membrane array. Comparative electron microscopy and X-ray diffraction will be used to examine heterogeneity of the myelin membrane lattice which occurs in certain pathological conditions or after chemical treatment. X-ray diffraction, electron probe, and atomic absorption spectrophotometer measurements on intact myelin and model lipid-protein system treated with heavy metal cations will help us to localize specific lipids and proteins within the membrane, and may elucidate mechanisms of metal toxicity involving the cell membrane. Studies using biophysical, chemical, and immunocytochemical techniques on isolated glial plasma membranes and on developing nerves from mutant animals with myelin protein abnormalities will provide information on membrane differentiation and assembly during myelin formation. This combined structural-chemical approach will help to elucidate the molecular processes involved in demyelinating diseases such as multiple sclerosis.